Antiprotozoal agents

Class Summary

Nitroimidazole antimicrobial. Generates radical species in both aerobic and anaerobic conditions that are capable of damaging parasitic DNA. Inhibits DNA, RNA, and protein synthesis within the T cruzi parasite. Studies suggest benznidazole is reduced by a type I nitroreductase (NTR) enzyme of T cruzi, producing a series of short-lived intermediates that may promote damage to several macromolecules, including DNA. Approved by the FDA for treatment of Chagas disease in children aged 2-12 years. The CDC recommends antiparasitic treatment for all cases of acute (ie, congenital) or reactivated Chagas disease and for chronic T cruzi in children up to age 18 years. The CDC also strongly recommends treatment for adults aged 50 years or younger with chronic infection who do not already have advanced Chagas cardiomyopathy.

Available only from the CDC Drug Service (Ph. 404‑639‑3670). Well absorbed by digestive tract. Trypanocidal drug that acts on circulating trypomastigotes, as well as intracellular amastigotes. The mechanism of action may depend on the formation of nitro anion radicals, but precise details are not known. Efficacy can be assessed by monitoring disappearance of T cruzi–specific antibodies, although this may take several years in some patients. Repeated PCR assay can be used to look for treatment failure.

Centers for Disease Control and Prevention. The Global Surveillance Network of the ISTM and CDC. The GeoSentinel Newsletter: Information for Action. Infrequent Diagnoses & Their Geographic Exposures. 2008.

Chagas disease (American trypanosomiasis). The trypomastigote is the infective flagellated form of the parasite found in the blood of the mammalian hosts (blood trypomastigote) and in the hindgut of vectors (metacyclic trypomastigote). Image courtesy of Peter Darben, MD.

Chagas disease (American trypanosomiasis). The epimastigote form of Trypanosoma cruzi is the multiplying stage of the parasite that grows in the gut of the insect vector and also in cell-free culture medium as shown here. Image courtesy of Peter Darben, MD.

Rhodnius prolixus, a common vector of Trypanosoma cruzi. Eggs, first- and second-stage nymphs, and adult.

Trypanosoma cruzi in heart muscle of a child who died of acute Chagas disease in Texas. (H&E, x900).

Chest radiograph of a Bolivian patient with chronic Trypanosoma cruzi infection, congestive heart failure, and rhythm disturbances. Pacemaker wires can be seen in the area of the left ventricle.

Barium swallow radiographic study of a Brazilian patient with chronic Trypanosoma cruzi infection and megaesophagus. The markedly increased diameter of the esophagus and its failure to empty are typical findings in patients with megaesophagus caused by Chagas disease. Courtesy of Dr. Franklin A. Neva, Bethesda, MD.

Air-contrast barium enema of a Bolivian patient with chronic Chagas disease and megacolon. The markedly increased diameters of the ascending, transverse, and sigmoid segments of the colon are readily apparent.

Footnote 1. Mexico, as well as all nations of Central and South America, are endemic for Chagas disease. Chagas disease is not endemic in any of the Caribbean Islands. Women who were born in Chagas endemic countries or who have resided therein for a substantial period are at geographic risk for having Chagas disease. In addition, women who are not themselves at geographic risk but whose mothers are at such a risk and are not known to be seronegative are in turn considered to be at risk for Chagas disease. Footnote 2. The two approaches useful in this regard are microscopic examination of anticoagulated blood and polymerase chain reaction (PCR). Serologic testing of newborns is not useful because assays for specific immunoglobulin G (IgG) will yield a positive result, reflecting the mother’s chronic infection, and because immunoglobulin M (IgM) assays lack acceptable levels of sensitivity and specificity. Footnote 3. All children born to at risk women should be tested serologically since several studies indicate that the rate of congenital Chagas disease in babies born to infected mothers is 2%-10%. Footnote 4. The latter should include periodic monitoring for signs and symptoms of chronic cardiac and gastrointestinal Chagas disease followed by appropriate interventions, when indicated. The usefulness of specific drug treatment in adults with chronic Trypanosoma cruzi infections has not been clearly demonstrated and is a matter of ongoing debate. Footnote 5. The parasitologic cure rate in babies with congenital Chagas disease approaches 100% when a full course of treatment is given during the first year of life. Footnote 6. The sensitivities of microscopic examination of anticoagulated blood and PCR are less than 100%. Thus, the occasional baby who tests negative in these approaches immediately after birth may actually be infected with T cruzi. Serologic testing for specific IgG should be delayed until maternal IgG has disappeared.

Disclosure: Received salary from Goldfinch Diagnostics Inc. for equity owner; Received royalty from Quest Diagnostics Inc. for licensed technology; Received royalty from Abbott Laboratories, Inc. for licensed technology.